Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction defined as the impaired ability of vascular endothelium to stimulate vasodilation plays a key role in the development of atherosclerosis and in various pathological conditions which predispose to atherosclerosis, such as hypercholesterolemia, hypertension, type 2 diabetes, hyperhomocyst (e) inemia and chronic renal failure. The major cause of the endothelial dysfunction is decreased bioavailability of nitric oxide (NO), a potent biological vasodilator produced in vascular endothelium from L-arginine by the endothelial NO synthase (eNOS). In vascular diseases, the bioavailability of NO can be impaired by various mechanisms, including decreased NO production by eNOS, and/or enhanced NO breakdown due to increased oxidative stress. The deactivation of eNOS is often associated with elevated plasma levels of its endogenous inhibitor, N(G) N(G)-dimethyl-L-arginine (ADMA). In hypercholesterolemia, a systemic deficit of NO may also increase the levels of low density lipoproteins (LDL) by modulating its synthesis and metabolism by the liver, as suggested by recent in vivo and in vitro studies using organic NO donors. Therapeutic strategies aiming to reduce the risk of vascular diseases by increasing bioavailability of NO continue to be developed. Cholesterol-lowering drugs, statins, have been shown to improve endothelial function in patients with hypercholesterolemia and atherosclerosis. Promising results were also obtained in some, but not all, vascular diseases after treatment with antioxidant vitamins (C and E) and after administration of eNOS substrate, L-arginine, or its cofactor, tetrahydrobiopterin (BH(4)). Novel strategies, which may produce beneficial changes in the vascular endothelium, include the use of natural extracts from plant foods rich in phytochemicals.
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PMID:Nitric oxide therapies in vascular diseases. 1181 65

Numerous epidemiologic and clinical studies have demonstrated a clear relationship between high salt intake and blood pressure. However, the mechanisms of a salt-induced increase in blood pressure--a phenomenon known as salt sensitivity--and the heterogeneity of this effect are far from being completely understood. Endothelial dysfunction, and especially the nitric oxide system, is implicated in both experimental and clinical hypertension. Animal studies indicate that endogenous nitric oxide plays an important role in renal hemodynamics and sodium homeostasis, inducing renal vasodilation and natriuresis. Studies of essential hypertensive patients have also suggested that both high salt intake and salt sensitivity are associated with impaired endothelial function. Although there are many hypotheses concerning the nature of salt sensitivity, clinical data indicate that salt-sensitive patients may be unable to up-regulate the production of nitric oxide in response to salt intake. This endothelial dysfunction, which is more frequent in salt-sensitive than in salt-resistant essential hypertensive patients, may partially explain the blood pressure increase in response to salt intake and may underlie the more pronounced target organ damage and cardiovascular risk in salt-sensitive patients.
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PMID:Salt intake, endothelial dysfunction, and salt-sensitive hypertension. 1182 36

Gene transfer may be appropriate for therapeutic protocols targeted at the vascular endothelium. Endothelial dysfunction is the principal phenotype associated with atherosclerosis and hypertension. Oxidative stress has been implicated in the development of endothelial dysfunction. We have explored the ability of overexpressing anti-oxidant genes (superoxide dismutases; SODs) in vitro and in vivo to assess their potential for reversing endothelial dysfunction in a rat model, the stroke-prone spontaneously hypertensive rat (SHRSP). Western blotting and immunofluorescence assays in vitro showed efficient overexpression of MnSOD and ECSOD with respect to localisation to the mitochondria and extracellular surface, respectively. Transgene functional activity was quantified with SOD activity assays. MnSOD and ECSOD overexpression in intact SHRSP vessels in vivo led to endothelial and adventitial overexpression. Pharmacological assessment of transduced vessels following in vivo delivery by basal NO availability quantification demonstrated that the "null" adenovirus and MnSOD adenovirus did not significantly increase NO availability. However, AdECSOD-treated carotid arteries showed a significant increase in NO availability (1.91 +/- 0.04 versus 0.75 +/- 0.08 g/g, n = 6, P = 0.029). In summary, efficient overexpression of ECSOD, but not MnSOD in vivo, results in improved endothelial function in a rat model of hypertension and has important implications for the development of endothelial-based vascular gene therapy.
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PMID:Adenovirus-mediated overexpression of extracellular superoxide dismutase improves endothelial dysfunction in a rat model of hypertension. 1185 69

Endothelial dysfunction can be observed in preatherosclerotic conditions. However, its pathogenetic role in hypertension is still controversial. Endothelial-dependent changes of blood pressure (BP) and expression of endothelial nitric oxide synthase (eNOS) were evaluated in cold-induced hypertensive rats. Wistar rats were exposed to cold stress for 8 weeks. Exposure to cold stress significantly increased the systolic BP in rats. The infusion of acetylcholine significantly lowered mean arterial BP in control rats by 48 +/- 2% and by 32 +/- 1% in cold-induced hypertensive rats. The acetylcholine-induced reduction of mean arterial BP was significantly attenuated in cold-induced hypertensive rats (control rats, 45 +/- 2 mm Hg; cold-induced hypertensive rats, 34 +/- 3 mm Hg; P < .05). Administration of N(G)-nitro-L-arginine-methyl ester for 1 week significantly increased BP in control rats, whereas no effect could be observed in cold-induced hypertensive rats. In cold-induced hypertensive rats eNOS in aortic vessels was significantly reduced compared to control rats. In this nongenetic, nonsurgical animal model of cold-induced hypertensive rats an endothelial dysfunction can be observed due to reduced eNOS.
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PMID:Endothelial dysfunction in cold-induced hypertensive rats. 1186 54

Endothelial dysfunction, considered as a defective vascular dilatation after certain stimuli, is characteristic of different pathological conditions, such as hypertension, atherosclerosis, or diabetes. A decreased synthesis or an increased degradation of nitric oxide (NO) has been postulated as the mechanism responsible for this alteration. The present experiments were designed to test the hypothesis that the presence of an abnormal extracellular matrix in vessel walls could be responsible for the decreased NO synthesis observed in these pathological conditions. Experiments were performed in cultured human umbilical vein endothelial cells (HUVECs) grown on type IV (Col. IV) or type I (Col. I) collagen. Cells seeded on Col. I showed decreased nitrite synthesis, nitric oxide synthase activity, eNOS protein content, and eNOS mRNA expression when compared with cells grown on Col. IV. Moreover, cells grown on Col. I failed to respond to glucose oxidase activation of the eNOS system. In both cases, the changes in the eNOS mRNA expression seemed to depend on the modulation of eNOS promoter activity. The downregulation of eNOS induced by Col. I was blocked by D6Y, a peptide that interferes with the Col. I-dependent signals through integrins, as well as by specific anti-integrin antibodies. Moreover, a decreased activation of integrin-linked kinase (ILK) may explain the effects observed in Col. I-cultured cells because the activity of this kinase was decreased in these cells and ILK modulation prevented the Col. I-induced changes in HUVECs. Taken together, these findings may contribute to explaining the basis of endothelial dysfunction in some vascular diseases.
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PMID:Decreased nitric oxide synthesis in human endothelial cells cultured on type I collagen. 1190 17

We investigated the role of insulin and glucose in the pathophysiology of hypertension associated with obesity. The comparative effects of an oral glucose load and of an L-arginine infusion on plasma glucose, plasma insulin and blood pressures (BP) were assessed in lean normotensive and in obese hypertensive males. Oral glucose (75 g in 1-2 min) induced a small but significant lowering of BP in lean normotensives, but failed to modify BP in obese hypertensives. L-arginine infusion (30 min, 500 mg/kg total dose) reduced BP; significantly greater reductions in systolic and diastolic BP were observed in obese hypertensives than in the control group. Both oral glucose and L-arginine induced greater increases in plasma insulin in obese hypertensives than in lean normotensives. Endothelial dysfunction which accompanies the insulin resistant state of obesity, glucose intolerance and hypertension, may account for the different BP effects induced by glucose and L-arginine in obese hypertensives and lean normotensives.
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PMID:Differential blood pressure effects of oral glucose and intravenous L-arginine in healthy lean normotensive and obese hypertensive subjects. 1198 11

Dialysis patients constitute a high-risk subset of patients for developing cardiovascular disease, which accounts for nearly 50% of deaths. After stratification for age, race and gender, cardiovascular mortality is 10-20 times higher in dialysis patients than in the general population. Cardiovascular disease in this population cannot be fully explained by the high prevalence of classical cardiovascular risk factors (age, hypertension, diabetes, hyperlipidemia, smoking, etc.). Thus, the involvement of "new" cardiovascular risk factors (hyperhomocysteinemia, hyperfibrinogenemia, high lipoprotein (a) levels, oxidative stress, inflammation, etc.), and uremia-related factors (anemia, impaired calcium-phosphorus metabolism, hyperparathyroidism, accumulation of endogenous inhibitors of nitric oxide synthesis, etc.) has been also invoked to play a role in the increased cardiovascular risk in these patients. Endothelial dysfunction is the initial event in the development of atherosclerosis. Uremic patients exhibit an endothelial dysfunction, even before starting dialysis, which persists o is even aggravated under dialysis treatment. Uremic patients must be considered at high risk of developing cardiovascular disease. Thus cardiovascular risk factors in these patients should be managed early, aggressive and multifactorially in order to reduce their high cardiovascular morbidity and mortality.
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PMID:[Cardiovascular risk in patients with chronic renal failure. Patients in renal replacement therapy]. 1198 73

Large and small arteries are remodelled in hypertension - their structure, function and mechanics are altered. These changes contribute to elevated blood pressure and to the complications of hypertension. The present paper concentrates on small (resistance) artery changes in hypertension. In hypertension, these vessels exhibit a form of remodelling known as 'eutrophic' remodelling, in which smooth muscle cells are restructured around a smaller lumen, without true hypertrophy, particularly in milder forms of hypertension. Changes in these small arteries are the first manifestation of target organ damage in patients with hypertension. In more severe forms of hypertension and in secondary hypertension, hypertrophic remodelling has been reported. Stiffness of the vessel wall may be decreased initially; later, as hypertension becomes more severe, the wall of resistance vessels may become stiffer. Endothelial dysfunction occurs in a percentage of patients, similar to the prevalence of left ventricular hypertrophy. Interruption of the renin-angiotensin system may correct many of these abnormalities. The present report investigated the effects of angiotensin type 1 (AT1) receptor antagonists on small arteries of hypertensive patients compared with the beta-blocker atenolol in different studies. Beta-blocker treatment did not modify either the structure or the function of small arteries in contrast to the AT1 antagonist losartan in a double-blind, randomized, one-year study. Patients previously treated with atenolol to lower blood pressure, but whose small artery structure and function did not improve, were examined. These hypertensive patients were switched to the AT1 antagonist irbesartan for one year. Gluteal subcutaneous biopsies showed that the structure and endothelial function of small arteries that had remained altered by atenolol treatment were corrected by irbesartan treatment, although blood pressure control with irbesartan was identical to that previously achieved with atenolol. Improved outcomes in clinical trials using angiotensin-converting enzyme inhibitors and AT1 receptor antagonists may be a result of the vascular protective effects offered by these agents.
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PMID:Vascular changes in hypertension in response to drug treatment: Effects of angiotensin receptor blockers. 1204 89

Erectile dysfunction (ED) is a common problem in the United States, with estimates that 30 million men suffer with some degree of ED. Although causes include psychogenic, organic, and mixed forms, in middle-aged and older men one of the most common causes is vascular disease. Endothelial dysfunction, even without definitive arterial stenosis, as well as atherosclerosis with definitive stenosis of blood vessels, contributes to the problem. Endothelial dysfunction and atherosclerosis of blood vessels that supply the penis are associated with the same cardiovascular risk factors that affect the coronary arteries: smoking, lipid abnormalities, hypertension, and diabetes.
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PMID:Erectile dysfunction and atherosclerosis. 1216 40

Endothelial dysfunction ensuing inhibition of nitric oxide synthase (NOS) was investigated in male Sprague-Dawley rats given N(omega)-nitro-L-arginine methyl ester (L-NAME) in drinking water for 8 weeks. Age-matched rats served as controls. L-NAME-treated rats, as compared to control animals, showed: (1) a clear-cut increase in systolic blood pressure; (2) a consistent decrease of endothelial-cell NOS (eNOS) gene expression in aortic tissue; (3) a reduction of the relaxant activity of acetylcholine (ACh, from 10(-10) to 10(-4) M) on norepinephrine-precontracted aortic rings (reduction by 52+/-5%); (4) a marked decrease (-50%) of the basal release of 6-keto-prostaglandin F(1 alpha) (6-keto-PGF(1 alpha)) from aortic rings. In L-NAME-treated rats, administration in the last 2 weeks of either the angiotensin-converting enzyme inhibitor enalapril (1 mg/kg/day) or the cognate drug quinapril (1 mg/kg/day) decreased systolic blood pressure levels, completely restored eNOS mRNA levels in aortic tissue, and allowed a consistent recovery of both the relaxant activity of ACh and the generation of 6-keto-PGF(1 alpha). No difference was present in the ability of the two angiotensin-converting enzyme inhibitors to reverse NAME-induced endothelial dysfunction. These findings indicate that L-NAME-induced hypertension in the rat relies on the marked impairment of the endothelial vasodilator function, with an ensuing contribution by a decreased production of prostacyclin by the endothelial cells. Angiotensin-converting enzyme inhibition by enalapril or quinapril was equally effective in improving endothelial vasodilator function, prostacyclin endothelial production and restoring aortic eNOS mRNA.
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PMID:Enalapril and quinapril improve endothelial vasodilator function and aortic eNOS gene expression in L-NAME-treated rats. 1217 10


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